ESTEVE, Drug Discovery and Preclinical Development, Parc Científic de Barcelona, Baldiri Reixac, 4-8, 08028 Barcelona, Spain.
Institute of Biomedicine (IBUB), Department of Chemical Engineering and Analytical Chemistry, Universitat de Barcelona, Martí i Franquès 1-11, 08028 Barcelona, Spain.
Eur J Pharm Sci. 2018 Sep 15;122:331-340. doi: 10.1016/j.ejps.2018.07.010. Epub 2018 Jul 10.
In the present study three different procedures have been compared for the determination of the lipophilicity of the unionized species (log P) of neutral, acidic, basic, amphoteric, and zwitterionic drugs. Shake-flask, potentiometric and chromatographic approaches have been assayed in a set of 66 representative compounds in different phases of advanced development. An excellent equivalence has been found between log P values obtained by shake-flask and potentiometry, while the chromatographic approach is less accurate but very convenient for screening purposes when a high-throughput is required. In the case of zwitterionic and amphoteric compounds, either for shake-flask and chromatographic methods, the pH has to be accurately selected in order to ensure the compound to be in its neutral form.
在本研究中，比较了三种不同的方法来测定未离解物种（log P）的亲脂性，这些化合物包括中性、酸性、碱性、两性和两性离子药物。在一组 66 种处于不同开发阶段的代表性化合物中，测定了摇瓶法、电位法和色谱法。摇瓶法和电位法得到的 log P 值之间具有极好的等效性，而色谱法虽然准确性较低，但在需要高通量筛选时非常方便。对于两性离子和两性化合物，无论是摇瓶法还是色谱法，都必须准确选择 pH 值，以确保化合物处于中性形式。
